RT info:eu-repo/semantics/article
T1 Antiparasitic effect of synthetic aromathecins on Leishmania infantum
A1 Reguera Torres, Rosa María
A1 Álvarez Velilla, Raquel
A1 Domínguez Asenjo, Bárbara
A1 Gutiérrez Corbo, María del Camino
A1 Balaña Fouce, Rafael
A1 Cushman, Mark
A1 Pérez Pertejo, Maria Yolanda
A2 Toxicologia
K1 Veterinaria
K1 Leishmania
K1 DNA-Topoisomerase IB
K1 Camptothecin
K1 Aromathecins
K1 3109 Ciencias Veterinarias
K1 32 Ciencias Médicas
AB [EN} Background Canine leishmaniasis is a zoonotic disease caused by Leishmania infantum, being the dogs one of the major reservoirs of human visceral leishmaniasis. DNA topology is a consolidated target for drug discovery. In this regard, topoisomerase IB – one of the enzymes controlling DNA topology – has been poisoned by hundreds of compounds that increase DNA fragility and cell death. Aromathecins are novel molecules with a multiheterocyclic ring scaffold that have higher stability than camptothecins. Results Aromathecins showed strong activity against both forms of L. infantum parasites, free-living promastigotes and intra-macrophagic amastigotes harbored in ex vivo splenic explant cultures obtained from infected BALB/c mice. However, they prevented the relaxation activity of leishmanial topoisomerase IB weakly, which suggests that the inhibition of topoisomerase IB partially explains the antileishmanial effect of these compounds. The effect of aromathecins was also studied against a strain resistant to camptothecin, and results suggested that the trafficking of these compounds is not through the ABCG6 transporter. Conclusions Aromathecins are promising novel compounds against canine leishmaniasis that can circumvent potential resistances based on drug efflux pumps.
PB BMC
LK https://hdl.handle.net/10612/17836
UL https://hdl.handle.net/10612/17836
NO Reguera, R. M., Álvarez-Velilla, R., Domínguez-Asenjo, B., Gutiérrez-Corbo, C., Balaña-Fouce, R., Cushman, M., & Pérez-Pertejo, Y. (2019). Antiparasitic effect of synthetic aromathecins on Leishmania infantum. BMC veterinary research, 15(1), 405. https://doi.org/10.1186/s12917-019-2153-9
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 14-may-2024